We often see programs reach FDA review where the outcome is largely defined by endpoint and comparator decisions made two to three years earlier.
—— Allan Huang
For biotech and pharmaceutical leaders, China is now a common starting point for clinical development. Faster study activation, access to large patient populations, and regulatory progress have made it a practical option for early-phase programs.
At the same time, sponsors pursuing FDA and EMA approvals are seeing a consistent issue: programs initiated in China often require additional bridging studies, revised comparators, or expanded datasets when moving toward Western registrations.
Many sponsors view these challenges as regulatory hurdles that emerge during submission preparation. In reality, they are usually the result of strategic decisions made years earlier regarding patient populations, endpoints, and comparators. By the time regulators raise concerns, the opportunity to address them efficiently has often passed.
This is fundamentally a strategy problem, not a regulatory problem. These issues can often be addressed through early global development planning, fit-for-purpose MRCT strategies, future-focused comparator selection, and predefined bridging approaches.
These issues are rarely due to execution. In most cases, they result from protocol design decisions made early that limit how the data can be used across regions.
Endpoint selection is another common constraint, particularly when surrogate endpoints are not accepted by Western regulators.
When programs are designed with both China and Western requirements in mind from the outset, they are more likely to progress without additional studies.
Where Alignment Matters Most
Regulatory Expectations Require Coordination
China’s NMPA has moved closer to ICH standards, but FDA and EMA expectations still differ in ways that affect trial design.
Differences often include:
- Clinical endpoint selection
- Comparator expectations
- Evidence required to support broader use
Protocols designed for one region often require changes or additional data to meet global requirements. Alignment needs to be addressed early.
We also see differences in acceptable control arms, especially where standard of care has evolved more rapidly in Western markets.
Population Strategy Affects How Data Is Used
China provides strong enrollment advantages. However, studies limited to a single geography raise questions about broader applicability.
Key considerations include:
- Differences in treatment response across populations
- Variations in clinical practice
- Need for bridging data
If these factors are not addressed early, additional studies are often required later, extending timelines and increasing cost.
We see this most frequently when studies are conducted in a single population without predefined plans for extrapolation.
The issue is rarely the data itself. The issue is whether the study was designed from the outset to support multiple regulatory pathways.
Including multiple regions earlier helps reduce these issues.
Endpoint and Comparator Choices Affect Approval Pathways
Two design decisions have a direct impact on global use:
- Endpoints, which must meet FDA and EMA expectations for clinical relevance
- Comparators, which must reflect current international standards of care
Misalignment in these areas is a common reason for delays in global programs.
Comparator selection is often the single biggest driver of additional studies in global development.
Once a study has started, these elements are difficult to change and often require new trials.
This is why endpoint and comparator decisions should be viewed as strategic choices rather than protocol details. They influence not only study design, but also the future regulatory and commercial path of the asset.
When aligned early, the same dataset can support multiple regulatory submissions.
Structuring for Parallel China–Global Pathways
Sponsors are moving away from sequential development toward parallel pathways that support China and Western markets at the same time.
In many therapeutic areas, sequential China-first approaches now lead to delays when programs expand globally. This is particularly evident in oncology, where competitive timelines leave little room for sequential development.
The objective is not to reduce China’s role in development. Rather, it is to ensure that decisions made to support Chinese registration also support future global approvals.
This approach maintains the advantages of China while increasing the likelihood that the data can support multiple regulatory submissions.
Engage Regulators Early
Early engagement with NMPA, FDA, and EMA helps align expectations before protocols are finalized:
- Agreement on endpoints
- Confirmation of comparators
- Alignment on study design
This reduces the likelihood that additional studies will be required later.
A common mistake is waiting until Phase III to engage FDA or EMA, when key design elements are already fixed.
Embed China Within an MRCT Framework
Instead of running standalone China studies, sponsors are incorporating China into multi-regional clinical trials (MRCTs):
- China contributes to enrollment scale
- Other regions support regulatory acceptance across multiple markets
- Predefined analyses address regional differences
This allows one study to support multiple regions.
Novotech applies this approach by combining operational depth in China and Asia-Pacific with execution capability in the United States and Europe, allowing China to drive enrollment without limiting global relevance.
In practice, this requires aligning site selection, protocol design, and operational delivery across regions from the start.
Design for the Target Markets
Programs that progress smoothly are designed based on where the drug will be approved—not just where the trial starts.
This includes:
- Endpoints aligned with FDA and EMA expectations
- Comparators reflecting current global practice
- Data that can be used across submissions
These decisions affect timelines and overall program efficiency.
We advise sponsors to define their primary regulatory pathway before finalizing endpoint and comparator strategy.
This Is Often an Execution Issue
The importance of global design is widely understood. Preserving design intent through execution is often more difficult.
This requires:
- Up-to-date understanding of regulatory expectations across regions
- Therapeutic expertise
- Consistent delivery across geographies
Programs often diverge at this stage when design intent is not maintained through execution.
Breakdown often occurs when protocol intent is interpreted differently across regions during execution.
In other words, a sound development strategy can still fail if the rationale behind key design decisions is not preserved throughout study delivery.
CRO selection plays a direct role here. The ability to carry design decisions through execution across regions determines whether a program stays on track or requires additional work.
The ability to carry design decisions through delivery is where many programs succeed or fail.
Enabling Global Development from a China Starting Point
Novotech’s approach connects regional strength with global development requirements.
With operational and regulatory expertise across Asia-Pacific, the United States, and Europe, we support programs where China is part of a broader global strategy.
In practice:
- Protocols are designed for multiple regulatory pathways from the start
- China contributes to enrollment within globally relevant trial structures
- Design and execution are aligned so that protocols are implemented consistently across regions
Many programs encounter challenges when the original design intent is not carried through execution. This is also where Novotech focuses its delivery model.
Our approach is to align regulatory, scientific, and operational teams from the outset so decisions hold through execution.
For sponsors pursuing both China and Western registrations, maintaining this continuity helps reduce the risk that early design decisions become obstacles later in development.
Takeaway
China will continue to play a central role in global clinical development. The focus now is ensuring that programs initiated there can support approvals across multiple regions.
Programs that align population, endpoints, and comparators early are more likely to:
- Avoid additional studies
- Maintain timelines
- Support broader regulatory submissions
For leadership teams, program outcomes are largely determined at the design stage, and delays are often linked to early decisions that did not account for global requirements.
In global development, the most expensive delays are often the result of decisions made before enrollment begins.
For sponsors pursuing global approvals, some of the most consequential regulatory decisions are made long before any regulator reviews the data.
Selecting the right development partner at this stage directly affects both timeline and outcome.